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Copyright 2014 by Hengameh Zahed ii Acknowledgements My PhD experience, like that of many, has been a journey of self discovery as well as a scientific one. I have been truly lucky to benefit from the help of many on this journey. First and foremost, I dedicate this thesis to my parents, Iran Sabet and Jalil Zahed, who gave up all material possessions, family ties, and social roots to move my siblings and me to the United States so we could pursue the best education and opportunities. Their dreams were large, their bravery unparalleled, and their dedication undeniable. I can never repay them for their sacrifices. I am also grateful to my parents for giving me two partners in crime to go through life with: my hard- working, brilliant, loving siblings, whose support I have relied so heavily on. My sister, Chakameh Zahed, is a perfect embodiment of a resilient mind meeting the most generous of souls. Thank you for being the older sister I could look up to and for helping me find the will to push through hard times. I learned to not shy away from a challenge watching you boldly become a talented and successful “EECS geek” and excel in a heavily male-dominated field. My brother, Hazhir Zahed, has been the voice of calm and reason throughout my life. I am impressed by your confidence and articulateness and have sought your wisdom time and again. From you I’ve learned that success is the end product of gracefully getting up every time you fall. Your drive and passion in everything you do is inspiring. I am so lucky to have you in my life. I also want to acknowledge the dedication and support of my best friend, my rock, my love: Erik Ko. None of this would be possible without you. You are the most patient, caring, and understanding human being I have ever met and the best partner I could ask for. From driving me to lab at 3am and sleeping on the couch while I wait for two hours to put the next plate on the microscope, to patiently weathering my ups and downs in lab, you made it possible for me to do this work. Sharing a laugh with you was sometimes the only thing that kept me going during a string of failed experiments. I can never thank you enough for everything you have done and continue to do for me! iii Scientifically, I will be forever grateful and indebted to my mentor, Steve Finkbeiner, for taking a chance on me and showing me patience. I have learned so much about the art of being a scientist from you: how to present effectively and memorably, craft a compelling manuscript, approach scientific problems, bring clarity to an idea, and get others excited about our work. Your creativity, dedication to the lab and to science, efficiency, brilliance, and quantitative approach to biology are examples I will aspire to. I am convinced you don’t sleep, because there can’t be enough hours in a day to accomplish all that you do. I am also grateful for your incredible ability to raise funds. To not have to worry about the cost of doing science during one of the worst funding cycles, when many other labs were struggling to even remain open, is a blessing I can’t over-emphasize. I will also always fondly remember your enthusiasm for Halloween and your hospitality, generosity, and masterful culinary skills so elegantly displayed during the yearly feasts at your home. Science is as much a team sport as an individual pursuit and I am indebted again to Steve for his ability to assemble the perfect team. During my time in the Finkbeiner lab, I was surrounded by an incredibly smart and inspiring group of people and I owe much of my development as a scientist to them. To say it has been a humbling experience is an understatement. The Finkbeiner lab truly has been a second home to me and I have formed so many friendships here that leaving the lab feels like a second migration. Montse Arrasate took me on as a rotation student and taught me everything I needed to know to get started. Working with her was a true joy. I’m not embarrassed to admit that I cried the day she left the lab. In addition to Montse, Gaia Skibinski, Julia Kaye, and Kelly Haston are my role models for being a successful female scientist. They are all forces to be reckoned with: smart, creative, efficient, and thorough, while being truly amazing lab citizens and looking after grad students like me. Gaia (a.k.a “Officer”) Skibinski, who I have never seen without a smile on, has been a dear friend to me inside and outside of the lab. We have shared so many coffee chats about lab and life, and I owe you so much. Your friendship and advice mean more than words can explain. Julia Kaye is a free spirit with a contagious passion for science, whom I have admired from the first day I met her. Thank you for always being iv willing to listen and to lend a hand with experiments. Kelly Haston has encouraged me to keep going both in the lab and on the running trail and has brightened many days with her humor. I am also fortunate enough to have had Sami Barmada as an exemplary model of a physician-scientist to look up to. I am grateful for the countless hours he let me shadow him in the clinic. Working on his dad jokes long before he even had a kid made for colorful moments. My friendship with Ashkan Javaherian started long before he joined the Finkbeiner lab. He was my first rotation mentor at UCSF in Arnold Kriegstein’s lab and I was thrilled when he joined Steve’s lab. Steve has also mentored many graduate students and I have benefitted significantly from overlapping with many of them. Julia Margulis is like a younger but wiser sister to me. We have shared so many happy memories these past years: wine-tasting, celebrating birthdays, singing our hearts out at karaoke, house- boating, sky-diving, exploring Tahoe and Vegas, and many more. Thank you for patiently listening to me during so many lunches and for being one of my closest confidantes. Ian Kratter and Aaron Daub were my MSTP brothers in lab. We joined Steve’s lab roughly around the same time, helped each other during the good and bad times, lent a hand for each other’s experiments, advised each other, and pushed each other through the program. Ian Kratter: thank you for never letting a moment in lab get dull with your singing, for enriching my life with discussions of science and politics, and for letting me pull pranks on you when we just needed a break. Aaron Daub: you are seriously the nicest human being I have ever met. Inside the lab, we all benefited from your engineering knowledge and mechanical know–how. You kept Robo2 going and answered my middle of the night calls about Robo2 emergencies with the utmost grace. You gave us the Matlab and Pipeline Pilot algorithms that we all used for data analysis. Outside the lab, our hikes, adventures, and dinners together were occasions to look forward to. Mike Ando: part friend, part neighbor, part lab mate, part geek extraordinaire. I will badly miss our “cookie o’clock” discussions of science. You were the technical genius behind Robo3 and our “Master MUG” (Microscope User’s Group). I and the rest of the lab owe you so much for your selfless efforts in keeping the microscopes running. Jason Miller (a.k.a Millerpedia or pizza-eating champion of the Finkbeiner lab): we all benefited v from your unapologetic curiosity. There was never a talk you didn’t raise your hand at with a thoughtful question, never a paper you hadn’t read, never a social or political subject you hadn’t thought about. Everything I know about microscopy I learned from him (or from Silvia Foppiano). You challenged us all to think more deeply and understand the methodology we use more thoroughly. Thank you for making me feel like the center of the universe every time we chatted, be it about lab or life, even though you always had so much going on. Eva Ladow was the source of so much knowledge in the lab, the molecular biology and protein chemistry guru we all went to. After Steve, she has been my role model for making beautiful, easily-understandable presentations on complex topics. Thank you for letting me crash on your couch, making us delicious lab-made ice creams and other yummy treats, and teaching me so much. Maya Chandru Overland and Carol Peebles—both witty, wicked smart, and graceful—have always been incredibly generous and open with their advice and their friendship. Erica Korb was a member of the “fun bay,” where we shared many laughs, especially when we proudly made the “stupid trophy” to make ourselves feel better about mistakes we inevitably all made. Thank you for encouraging me to say no when needed. There are many more brilliant people who I overlapped with in Steve’s lab and learned something from every single one of them: Amanda Mason, Adam Ziemann, Andrey Tsvetkov, Matthew Campioni, Lisa Elia, Rebecca Aron, Ana Osoria Oliveria, Jeannette Osterloh, Annie Wang, Kurt Weiberth, Arpana Arjun, Hong Joo Kim, Punita Sharma, Tina Tran, Andre Zandona. There is not enough space in these pages to thank them all the way I should.